Release of cysteinyl leukotrienes with aspirin stimulation and the effect of prostaglandin E-2 on this release from peripheral blood leucocytes in aspirin-induced asthmatic patients

Background The decrease in prostaglandin E-2 (PGE(2)) release due to aspiri n (ASA)induced cyclooxygenase inhibition and the increment in cysteinyl leu kotriene (Cys-LT) release secondary to the removal of the inhibitory effect of PGE(2) on Cys-LT release have been suggested in the pathogenesis of asp irin-induced asthma (AIA). Objective In this study, we aimed to investigate the in vitro release of Cy s-LT and to determine the effect of PGE(2) on Cys-LT release from periphera l blood leucocytes of patients with AIA after stimulation by ASA. Patients and methods Patients with AIA (n = 13), patients with ASA-tolerant asthma (ATA) (n = 12) and healthy volunteers as controls (n = 13) were inc luded to the study. ASA and PGE(2) at three different concentrations were a pplied to the peripheral blood leucocytes of the study group, and Cys-LT le vels following stimulants were assessed by enzyme immunoassay method. Results There was no difference in baseline Cys-LT levels between groups (A IA 353.4 +/- 55.5 pg/mL, ATA 354.7 +/- 40.3 pg/mL, and control group 368.5 +/- 30.2 pg/mL; P > 0.05). Though not present in other groups, the Cys-LT l evel of 453.6 +/- 70.0 pg/mL following ASA stimulation was higher than base line in patients with AIA (P = 0.04). When PGE2 was added to the ASA-stimul ated samples of patients with AIA, Cys-LT levels were measured as 298.7 +/- 78.6 pg/mL, 279.8 +/- 79.9 pg/mL, and 243.4 +/- 51.3 pg/mL at PGE(2) 10(-7 ) M, 10(-6) M and 10(-5) M concentrations, respectively. These levels were lower than the ASA-stimulated Cys-LT values (P = 0.03, P = 0.01 and P = 0.0 1, respectively). The inhibitory effect of different PGE(2) concentrations on Cys-LT release was also present in patients with ATA and in controls. Conclusion The increase in Cys-LT levels following ASA stimulation seems to be unique to AIA, which was not present in patients with ATA and in health y controls. The inhibitory effect of PGE(2) on stimulated Cys-LT levels is another important finding to elucidate the role of PGE(2) in the pathogenes is of AIA.